The project goals are: 1) to determine biomechanical properties of knee joint cartilage subjected to joint disuse (JD), disuse followed by ad libitum recovery (JD+R), disuse followed by excessive exercise (JD+E) and from the Pond-Nuki procedure for osteoarthritis (OA); 2) to determine biochemical composition and proteoglycan polydispersity for the same groups, and 3) to use the coefficients form the most appropriate theoretical constitutive models to describe relationships between biochemical and biochemical changes. The two fundamental questions we seek answers for are: 1) why do early atrophic changes in joint cartilage appear to be reversible, and 2) why do early OA changes in joint cartilage appear to be irreversible? "Disuse" of the knee will be induced by preventing weight bearing for specified periods of time, excessive exercise will be achieved by a specified treadmill exercise regime, and the Pond- Nuki model for OA will be achieved by anterior cruciate ligament resection. The biomechanical properties to be determined include: intrinsic tensile and compressive moduli, tensile strength, kinetic swelling properties (including the equilibrium Donnan osmotic pressure), permeability, and the intrinsic viscoelastic shear properties of specimens from high and low weight bearing areas. Joint contact areas (defining high and low weight bearing areas) will be determined by our new method to generate a computer graphics model of the joint anatomical surfaces and a computer program simulating articulation. Biochemical studies will include characterization of the proteoglycan aggregates recovered by dissociative methods from different depths and weight bearing areas of the cartilage surface. Of particular interest is the fate of the two aggregate proteoglycan populations isolated by our rate zonal centrifugation method, and the aggregating capacity of monomers from JD JD+R, JD+E, and OA tissues.